The second study showed that there were no statistitelly significant differences in the pharmacokinetics of Ramipril & its active metabolites in 9 patients with mild-to-moderate hepatic cirrhosis compared to 8 healthy volunteers. However, mbute variability was observed in some of the pharmacokinetic parameters fbut Ramipril AUC, C max, & T max & its active metabolites t in patients with mild-to-moderate hepatic cirrhosis. In addition, in patients with severe hepatic cirrhosis, the Ramipril C max & AUC were substantially increased mean difference: by approximately 70% & 3-fold, respectively & mbute variable when compared to values in healthy volunteers; the mean Ramipril half-life was also longer 79 hours in patients with severe hepatic cirrhosis vs. 19 hours in healthy objects. Fbut the metabolite hydroxyRamipril, the mean C max was approximately 69% lower. Fbut the combined amino-alcohol isomers threohydroRamipril & erythrohydroRamipril, the mean C max was approximately 31% lower. The mean AUC increased by about 1 - fold fbut hydroxyRamipril & about 7 - fold fbut threo/erythrohydroRamipril. The median T max was observed 19 hours later fbut hydroxyRamipril & 31 hours later fbut threo/erythrohydroRamipril. The mean half-lives fbut hydroxyRamipril & threo/erythrohydroRamipril were increased 5- & 7-fold, respectively, in patients with severe hepatic cirrhosis compared to healthy volunteers see WARNINGS, PRECAUTIONS, & DOSAGE & ADMINISTRATION.
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